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Contemporary Management of Ocular

Inflammation and Allergy

Jimmy D. Bartlett, O.D., D.Sc., FAAOPresident, PHARMAKON Group

Birmingham, Alabama

Disclosure Statement Alcon

Allergan

Bausch & Lomb Pharmaceuticals

PHARMAKON Group

United States Pharmacopeia (USP)

Wolters Kluwer Health

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Antiinflammatory Medications

Topical (ocular and dermatologic) corticosteroids

Oral corticosteroids

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Topical antihistamines

Oral antihistamines

Mast cell inhibitors

Topical immunosuppressive drugs

Steroid Formulations Over The Years

Importance of Shaking Steroid Suspensions

Patient Compliance With Shaking

Apt L, Henrick A, Silverman LM. Patient compliance with use of topical ophthalmic corticosteroid suspensions. Am J Ophthalmol. 1979;87(2):210-4.

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Dose Uniformity With Upright Storage and No Shaking

Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednateophthalmic emulsion 0.05% versus branded and generic prednisolone acetate ophthalmic suspension 1%. Clin Ophthalmol. 2010 Oct 5;4:1119-24.

Dose Uniformity With Upright Storage After 5 Sec of Shaking

Dose Uniformity With Inverted Storage and No Shaking

Percentage of Doses Within 15% of Declared Concentration

Usage Condition

Pred Forte GenericPrednisolone

Durezol

Upright, not shaken

54% 13% 100%

Upright, shaken 40% 6% 100%

Inverted, not shaken

0% 4% 100%

Stringer W, Bryant R. Dose uniformity of topical corticosteroid preparations: difluprednateophthalmic emulsion 0.05% versus branded and generic prednisolone acetate ophthalmic suspension 1%. Clin Ophthalmol. 2010 Oct 5;4:1119-24.

“No Shake” Steroid Options

Prednisolone phosphate 1.0% (solution)

Difluprednate (Durezol) (emulsion)

Loteprednol (Lotemax) (gel)

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What If My Patient Just Isn’t Getting Any Better? Is the patient shaking the suspension?

Did you pulse dose?

Did the pharmacist dispense generic pred?

Did the pharmacist dispense (illegally) generic FML?

Does the patient have steroid-induceduveitis?

Steroid-Induced Uveitis

First observed in steroid provocative studies in glaucoma

Incidence is higher in African-Americans (5%) than in caucasians (0.5%)

Symptoms include pain, photophobia, ciliaryflush, anterior chamber cells and/or flare

Treat by discontinuing or reducing steroid and substituting NSAID

Krupin T, et al. Uveitis in association with topically administered corticosteroid. Am J Ophthalmol. 1970;70(6):883-5.Martins JC, et al. Corticosteroid-induced uveitis. Am J Ophthalmol. 1974;77(4):433-7.

When Starting Steroid Therapy, What Dosage Frequency Should Generally Be Used?

A. TID

B. QID

C. Q 1-2 H

D. I would prefer to use more than C, if only the patient would comply

I would prefer to use more than C, if only the patient would

comply

HOW TO USE STEROIDS In a word, “Boldly!”

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Dosing Frequency and AntiinflammatoryEffect of Pred Forte

Dosage Total # Drops Inflammation

1 gt q 4h 6 11%

1 gt q 2h 10 30%

1 gt q h 18 51%

1 gt q 30 min 34 61%

1 gt q 15 min 66 68%

1 gt q min x 5 min q h

90 72%

Leibowitz HM, Kupferman A. Int Ophthalmol Clin 1980; 20: 117-134.

Topical Ocular Steroids

Topical Ocular Steroids

Prednisolone

Dexamethasone

Fluorometholone

Loteprednol

Rimexolone

Difluprednate

A sorry excuse for an ophthalmic steroid!!

Current Classification of Ocular Steroids

Ester-based

Loteprednol

Ketone-based

Prednisolone

Dexamethasone

Fluorometholone

Rimexolone

Difluprednate

Prednisolone Products

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Generic Versus Brand Name Steroids

Avoid generic Pred Forte (drug clogs bottle tip)

What About Omnipred?

New milling process that standardizes particle size to < 1 µm

Head-to-head comparison with PredForte

Raizman MB, Donnenfeld ED, Weinstein AJ. Clinical comparison of two topical prednisoloneacetate 1% formulations in reducing inflammation after cataract surgery. Curr Med Res Opin2007; 23: 2325-2331.

Is Pred Forte Still the “King” of Steroids?

DIFLUPREDNATE 0.05% (DUREZOL)

Difluprednate 0.05% (Durezol)

Emulsion vehicle

Preserved with sorbicacid

FDA approved for anterior uveitis, and inflammation and pain associated with ocular surgery

Durezol Emulsion Formulation

100 nm Water phase

Surfactant

Difluprednate (dissolved in oil)

Oil phase

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Resolution of PseudophakicCME in 63 yoBF

Chalam K, Khetpal V, Patel CJ. Spectral domain optical coherence tomography documented rapid resolution of pseudophakic cystoid macular edema with topical difluprednate. ClinOphthalmol. 2012;6:155-8.

Resolution of PseudophakicCME in 63 yoBF

Chalam K, Khetpal V, Patel CJ. Spectral domain optical coherence tomography documented rapid resolution of pseudophakic cystoid macular edema with topical difluprednate. ClinOphthalmol. 2012;6:155-8.

Study Design

Durezol 0.05%

Pred Forte 1%

Days 0 – 13Treatment Period

Days 14 – 20 Days 21 – 24 Days 25 – 27 --------------------------Tapering Period---------------------------

8x/day

• Tapering/safety period Days 28-42 - tapering at investigator’s discretion

• Durezol study group masked using vehicle drops

QID

BID

QD

QID

BID

QD

QOD

Clearing of Anterior Chamber Cells

(Grade 0 defined as ≤1 cell)

Conclusions

Durezol dosed QID was not inferior to PredForte dosed eight times a day

Durezol may offer increased patient compliance QID dosingEmulsion formulationBAK free

But IOP elevation is common

Foster CS, et al. Durezol (Difluprednate ophthalmic emulsion 0.05%) compared with Pred Forte 1% ophthalmic suspension in the treatment of endogenous anterior uveitis. J Ocul Pharm Ther2010; 26: 475-483.

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Complications of Durezol in Pediatric Uveitis IOP elevation ≥10 mm Hg and IOP ≥ 24

mm Hg was seen in 50% of eyes 3 eyes of 2 patients required glaucoma

surgery Cataract formation or progression occurred

in 39% of eyes 5 eyes of 3 patients required cataract

surgerySlabaugh MA, Herlihy E, Ongchin S, van Gelder RN. Efficacy and potential complications of difluprednate use for pediatric uveitis. Am J Ophthalmol.2012;153(5):932-8

STEROID-INDUCED OCULAR HYPERTENSION

Interesting Facts

Occurs in both healthy and glaucomatous eyes

Develops in 2-8 weeks

More prevalent with topical ketone-based steroids

Dissipates within one week after steroids are discontinued

Incidence of IOP Response

One-third of general population are “steroid responders” (≥ 3 mm Hg)

7-8% are “high” responders (≥ 10 mm Hg)

Patients Predisposed to IOP Response

Patients with POAG

Close relatives of patients with POAG

Children under 10 years of age

Steroids With Less Propensity to Elevate IOP Rimexolone (Vexol) Fluorometholone (FML) Loteprednol (Lotemax, Alrex)

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Topical Ophthalmic SteroidsEster-based

Loteprednol

Ketone-based

Prednisolone

Dexamethasone

Fluorometholone

Rimexolone

Difluprednate

Loteprednol Etabonate 0.5%The Only Ester-based Steroid

1. Bodor N. Pharmazie. 2001;56(suppl):S67-S74.2. Howes J, Novack GD. J Ocul Pharmacol Ther. 1998;14:153-158.

3. Holland EJ. Refract Eyecare. 2005;9(suppl):17-19.

HO

CH3

O

OHCH3

CH3

CH3

HO

O

OCH2CI

OCO2C2H5

C = O

Position 20ChloromethylEster

Position 20Hydroxymethyl KetoneC = O

CH2OH

LoteprednolEtabonate

Prednisolone

“Soft Steroid” Means Soft on Side Effects, Not Less Efficacy

What Impact Does LoteprednolEtabonate 0.5% Have on

Intraocular Pressure?

LE 0.5% IOP Response in Known Steroid Responders

Bartlett JD, et al. J Ocul Pharmacol Ther 1993;9:157-165

27.1 mm HgPrednisolone acetate 1.0%

21.5 mm HgLoteprednol etabonate 0.5%

Clinical Management of Steroid-Induced Ocular Hypertension Baseline IOP before treatment

Monitor IOP every 1-2 weeks

Risk is greatest in first 4-6 weeks

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What To Do About It

Discontinue steroid or reduce dosing frequency

Reduce steroid concentration (↑ cost)

Change to FML or Lotemax (↑ cost)

Treat with topical ocular hypotensive agents

Avoid

Prostaglandins

Pilocarpine

Loteprednol EtabonateFormulation Conc. (%) Trade Name

Suspension 0.5 Lotemax

0.2 Alrex

Ointment 0.5 Lotemax

Gel 0.5 Lotemax

Suspension vs Gel Viscosity

Shear forces from blinking

Electrolyte exchange from tears

Two mechanisms cause gel to immediately thin in the eye

Interesting Facts About The Gel

No shaking required except for initial “flick” to get it into dropper tip

Essentially no blurred vision in clinical trials

pH 6.5 vs 5.5 for suspension

Specified in grams, not milliliters

5g in 10 ml bottle

Pharmacist may dispense ung instead of gel

Rajpal RK, Roel L, Siou-Mermet R, Erb T. Efficacy and safety of loteprednol etabonate 0.5% gel in the treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2013; 39(2):158-67.

Prescription for Lotemax Gel

Lotemax Ophthalmic Gel 0.5%

# 5gmSig: One drop OD q2h while awake x 24 hr, then 4 times daily

None

STEROIDS AND CATARACT FORMATION

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Appearance of Steroid-Induced Cataract

• Posterior subcapsular

• Cannot be differentiated from early complicated cataract, radiation cataract or age-related posterior subcapsular cataract

Mechanism of Steroid-Induced Cataract Formation Formation of Schiff base intermediates

between the steroid C-20 ketone group and nucleophilic groups such as ε-amino groups of lysine residues of lens proteins

More Frequent with NonocularSteroids Oral

Inhaled

NOT intranasal

Interesting Facts About Steroid-Induced Cataracts Usual time to onset is 1 year with 10 mg/day of

prednisone (but can occur in a little as 2 months on 5 mg/day)

Incidence of oral steroid cataract is 6% to 39% Strong association between inhaled steroids and

PSC cataract No clear association between intranasal steroids and

PSC cataract Loteprednol (Lotemax) does not cause cataracts Individual susceptibility (Hispanics)

THERAPEUTIC INDICATIONS FOR

STEROIDS

Fundamental Steroid Guidelines

Choose steroid For short-term or IOP no concern

Pred Forte, Durezol, or Lotemax For long-term or IOP a concern

LE 0.5%, LE 0.2%, FML, or Vexol Pulse-dose Monitor IOP in first 2-6 weeks NO REFILLS! Use shortest effective course of therapy Avoid in presence of epithelial HSV, mycobacterial,

and fungal infection

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Infiltrative Keratitis/CLARE

CLARE

Initially thought to be primarily due to hypoxia

An inflammatory response to toxins produced by less virulent strains of gram negative bacteria

Recurrent episodes common

CLARE is NOT a marker for microbial keratitis

Sweeney, et al. Eye Contact Lens 2007

Differential Diagnosis of Corneal Ulcers vs. Sterile Infiltrates

Ulcer (MK) Rare

Usually painful

Tend to be central

1 to 1 staining defect to lesion ratio

Cells in anterior chamber

Generalized conjunctivalinjection

Usually solitary lesion

Possible tear lake debris

Eyelid swollen

Infiltrate

Common

Mild pain

Tend to be peripheral

Staining defect size relatively small

No cells in anterior chamber

Sector skewed injection pattern

Can be multiple lesions

Clear tear lake

Eyelid not swollen

Infiltrate

Common

Mild pain

Tend to be peripheral

Staining defect size relatively small

No cells in anterior chamber

Sector skewed injection pattern

Can be multiple lesions

Clear tear lake

Eyelid not swollen

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Management of CLARE

Topical steroid alone If cornea is clear/no epithelial

compromise Combination antibiotic/steroid

Pulse-dose q2h for 1-2 days, then q.i.d. for 4-5 days

Address CL hygiene and wearing time: Daily wear only!Otherwise, CLARE is likely to recur

Preferred Antibiotic-Steroid Combos

Steroids in Microbial Keratitis

Steroids for Corneal Ulcers Trial (SCUT)

Srinivasan M, et al. Arch Ophthalmol 2012;130(2):143-150.

SCUT Conclusions

“Conclusions: We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers.”

“Application to Clinical Practice: Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers.”*

*Exceptions: Patients with “finger counting” VA or worse at baseline, and patients with completely central ulcers.

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GPC

1. Asbell P et al. CLAO J. 1997:23:31-36.2. Friedlaender MH et al. Am J Ophthalmol. 1997;123:455-464.

3. Data on file, Bausch & Lomb Incorporated, 1994.

Giant Papillary Conjunctivitis

Significant improvement in primary clinical signs and symptoms

ResponseNumber of Patients Papillae Itching

Lens Intolerance

Loteprednol etabonate 0.5% 221 76% 94% 91%

Placebo 222 51% 79% 78%

P value <.001 <.001 <.001

Management of GPC

Discontinue contact lens wear if possible

If not, use daily disposables

Lotemax QID x 1-4 wks (no taper)

No other classes of drugs are necessary

Educate patient on CL hygiene, wearing schedule, etc.

Lotemax for Treatment of Dry Eye Inflammation Lotemax was compared with placebo for

treatment of the inflammatory component of dry eye

Randomized, double-masked, placebo-controlled, multicenter comparison

Patients with dry eye (n=66) 32 patients treated with Lotemax 34 patients treated with placebo

Subjects received either Lotemax or placebo QID in both eyes for 4 weeks

Pflugfelder SC, Maskin SL, Anderson B, et al. Am J Ophthalmol 2004; 138: 444-57.

Lotemax for Treatment of Dry Eye Inflammation When used as monotherapy, Lotemax resulted in

greater improvement in objective signs and symptoms of dry eye than placebo at both 2 and 4 weeks

Lotemax demonstrated no clinically significant IOP elevation following 1 month of therapy

Pretreatment with Lotemax prior to cyclosporine treatment showed: 75% lower stinging rate 68% lower rate of discontinuation with

cyclosporine therapySheppard JD, et al. Topical loteprednol pretreatment reduces cyclosporine

stinging in chronic dry eye disease. J Ocul Pharmacol Ther. 2011;27:23-7

Recommended Treatment Approach for Dry Eye Inflammation

Lotemax® QID(loteprednol etabonate ophthalmicsuspension 0.5%)

Artificial Tears

Lotemax® BID(loteprednol etabonate ophthalmicsuspension 0.5%)

Lotemax®…up to QID for flare-ups(loteprednol etabonate ophthalmicsuspension 0.5%)

Restasis® BID(cyclosporine ophthalmic emulsion) 0.05%)

Thereafter

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OCULAR ALLERGY

Treatment of acute ocular surface and eyelid inflammation in an atopic,

pregnant female

PATIENT: 32 YEAR-OLD AFRICAN-AMERICAN FEMALE

32 Year-Old AA Female

“This morning I was having a permanent in my hair”

“Some of the solution dripped into my eyes”

“My eyes immediately swelled and are extremely itchy. They are so swollen, I can hardly see.”

4 months pregnant

Has asthma and eczema, and so does her father

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Oral Antihistamines for ACUTEAllergic Angioedema

What is the Best (Safest) Allergy Treatment During Pregnancy?

Generic Name Trade Name Pregnancy Category

Dosing Frequency

Alcaftadine Lastacaft B QD

Nedocromil Alocril B BID-QID

Lodoxamide Alomide B QID

Cromolyn sodium Opticrom, Crolom B QID

Chlorpheniramine Chlor-Trimeton B QID

Loratadine Claritin B QD

Cetirizine Zyrtec B QD

Avoid Oral Antihistamines for Long-Term Therapy

Potential Issues

Elevated blood pressure when used with decongestants

Dry eye

Why Do Antihistamines Cause Dry Eye?

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Parasympathetic (Cholinergic) Innervation of Lacrimal Gland

Antihistamines

• H1 blockers reduce both aqueous and mucinproduction

• As little as 4 mg daily of chlorpheniramine maleate can produce positive Schirmer test

• Four days of once-daily loratadine (Claritin) can induce dry eye and corneal staining

• Can aggravate underlying condition of dry eye

Case Report Ocular Allergy: Epidemiology

90% ‐ 95%

SAC/PAC: Diagnosis Hallmark symptom: ITCHING! ± redness, lid swelling, chemosis Other factors distinguishing allergy from

viral/bacterial conjunctivitis:Pink conjunctiva (not red)Quality of discharge

SAC/PAC: stringy, ropeyBacterial: purulentViral: watery

SAC/PAC: Management Counsel patients to avoid allergens

Stay indoors during peak pollen daysMinimize ocular exposure

Wash hair before going to bed Palliative measures

Artificial tearsCold compresses

Determine how aggressively to treat based on severity of signs and symptoms

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Therapeutic Options

Medications for Allergic Conjunctivitis

Two Recent Paradigm Shifts Toward more targeted anti-

inflammatory therapy and rapid symptom relief

Away from systemic antihistamines for seasonal allergiesCause dry eye and ↑ ocular

symptomsTopical for ocular symptoms ICS or intranasal steroid for

nasal/sinus symptoms

Two Recent Paradigm Shifts Toward more targeted anti-

inflammatory therapy and rapid symptom relief

Away from systemic antihistamines for seasonal allergiesCause dry eye and ↑ ocular

symptomsTopical for ocular symptoms ICS or intranasal steroid for

nasal/sinus symptoms

Steroids in Asthma Management

SAC/PAC: Management ProtocolSymptoms Signs Treatment

Level 1 Mentions allergy symptoms only incidentally; not the primary complaint

Minimal or no signs

Palliative measures; Possibly antihistamine/ mast cell stabilizer

Level 2 Primary reason for visit is itching/other symptoms; Lifestyle is affected

Minimal or no signs

Topical steroid q.i.d. for 2 weeks, then b.i.d. for 1-2 months, then switch to anantihistamine/mast cell stabilizer if symptoms persist

Level 3 Primary reason for visit is itching/other symptoms; Lifestyle is greatly affected

Red eyes; conjunctival congestion or chemosis

Topical steroid q.i.d. for 2 weeks, then b.i.d. for 1-2 months, then switch to an antihistamine/mast cell stabilizer

Level 2

Level 3

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Steroids in SAC Management No longer considered a last resort Limit therapy to ester-based steroids (loteprednol) Use when there are significant signs or more severe

symptoms In severe cases, dosing can be increased to q2 h for the

first 2-3 days (while awake) Schedule follow-up at 3-4 weeks to check IOP and

therapeutic response No adverse effects reported with up to 4,000 doses of

Alrex over 36 months* IOP spikes can rarely occur

*Ilyas ,et al. Eye Contact Lens 2004;30:10-13.Lu E, Fujimoto LT, Vejabul PA, Jew RL. Steroid-induced ocular hypertension with loteprednoletabonate 0.2%--a case report. Optometry. 2011;82(7):413-20

When Using an AH/MCS, Which Dosing Frequency is Better:

QD or BID?“Which is better, 1 or 2?”

AH/MCS Treatment Options by Dosing Frequency

Twice daily

Bepreve

Elestat

Optivar

Patanol

Ketotifen(Zaditor, etc.)

Once daily

Bepreve

Pataday

Lastacaft

Williams JI, et al. Prolonged effectiveness of bepotastine besilate ophthalmic solution for the treatment of ocular symptoms of allergic conjunctivitis. J Ocul Pharmacol Ther. 2011; 27(4):385-93.

McCabe CF, McCabe SE. Comparative efficacy of bepotastine besilate 1.5% ophthalmic solution versus olopatadine hydrochloride 0.2% ophthalmic solution evaluated by patient preference. ClinOphthalmol. 2012;6:1731-8

Ocular Itch Relief, AM vs PM Nasal Itching and Rhinorrhea

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Overall Preference for Next Rx Product Comparisons

Lastacaft has effects on itching and redness similar to olopatadine 0.1% (Patanol)

OTC ketotifen is comparable to olopatadine 0.1% (Patanol) in reducing itching associated with SAC, although possibly somewhat less comfortable

Greiner JV, Edwards-Swanson K, Ingerman A. Evaluation of alcaftadine 0.25% ophthalmic solution in acute allergic conjunctivitis at 15 minutes and 16 hours after instillation versus placebo and olopatadine 0.1%. Clin Ophthalmol 2011;5:87-93.Leonardi A, Zafirakis P. Efficacy and comfort of olopatadine versus ketotifen ophthalmic solutions: a double-masked, environmental study of patient preference. Curr Med Res Opin2004;20:1167-1173.

Distinguishing Features of AH/MCSs Patanol

FDA approved for “redness” Bepreve

May offer improvement of nasal congestion and rhinorrhea

Available in 10 ml bottle/one copay Lastacaft

The safest for use during pregnancy Ketotifen

OTCTorkildsen GL, et al. Bepotastine besilate ophthalmic solution for the relief of nonocularsymptoms provoked by conjunctival allergen challenge. Ann Allergy Asthma Immunol.2010;105(1):57-64

Most eye allergy drugs are approved for “itching”… what can we do about the

redness?

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Two Pharmacologic Options

Decongestant (α1 receptor agonist)

Disadvantage: rebound hyperemia

Anti-inflammatory (corticosteroid or NSAID)

Disadvantage of steroids: IOP elevation and cataract formation

Disadvantage of NSAIDs: stinging, less effective

Topical Ocular Decongestants (α1 Receptor Agonists)

Generic Name Trade Name Duration (hr) Dosage

Phenylephrine HCl*

Relief 0.5-1.5 QID

Naphazoline HCl Naphcon 3-4 QID

Oxymetazoline Visine LR 4-6 Q6H

TetrahydrozolineHCl

Visine 1-4 QID

*More rebound hyperemia than others

Antihistamine-Decongestant Combos Naphazoline/pheniramine

Naphcon-A Visine-A Opcon-A

Dosing frequency is QID

Phospholipase A2

ActivityArachidonic Acid

LipoxygenasePathway

CyclooxygenasePathway

Mast CellMembrane

Phospholipids

HHT, MDA

Hydroperoxides(5-HPETE)

Leukotrienes(SRS-A, LTB4)

Prostaglandins(PGF2α, PGD2, PGE2)

Prostacyclin(PGI2)

Thromboxane A2

(TXA2)

HeparinHistamine PAFProteases (tryptase, chymase)

NSAIDsWork Here

Antihistamines1

Work Here

Most Combination Antihistamines/MCS1

Work Here

Late-PhaseMediators

Early-PhaseMediators

Slonim CB. Rev Ophthalmol. 2000:101-112.

Pharmacologic Intervention in the Inflammatory Cascade

CorticosteroidsMast Cell Stabilizers (MCS)1

Work Here

Loteprednol 0.2% (Alrex)

Approved for SAC

Pulse-dose, then QID

Taper ?

Pregnancy category C

Can be used safely for many months

How Safe is Alrex in Allergic Conjunctivitis?

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Long-Term Safety Study

Retrospective, multi-center 397 patients

54 on Alrex from 6 mo to 1 yr 159 on Alrex for > 1yr

Drops/eye ranged from 120 to 3741 No adverse findings

no IOP rise no cataract formation no exacerbation of an infectious disease

Ilyas H, et al. Eye Contact Lens. 2004;30:10-13.

Recent Prices for Prescription Ocular Allergy Drugs Patanol

$131/5ml

Pataday

$127/2.5ml

Lastacaft

$112/3ml

Bepreve

$118/5ml, $210/10ml

OTC Ketotifen 0.025% Products

Zaditor (Novartis) Alaway (Bausch & Lomb) Refresh Eye Itch Relief (Allergan) Ketotifen (Alcon, Apotex, Akorn) Claritin Eye Allergy Relief $12-15/10ml

(Alaway) Torkildsen GL, Abelson MB, Gomes PJ. Bioequivalence of two formulations of ketotifenfumarate ophthalmic solution: a single-center, randomized, double-masked conjunctival allergen challenge investigation in allergic conjunctivitis. Clin Ther 2008;30:1272-1282.

OTC Ketotifen in Children

Excellent treatment option for children

Inhibits their ocular itching as well as reduces redness, chemosis, and lid swelling

No untoward drug-related systemic events

Adverse ocular effects are insignificant

Abelson MB, Ferzola NJ, McWhirter CL, Crampton HJ. Efficacy and safety of single- and multiple-dose ketotifen fumarate 0.025% ophthalmic solution in a pediatric population. Pediatr Allergy Immunol 2004;15:551-557.

Contact Allergy Type IV reaction

Suspect contact allergy if

No history of allergy

Lower lid and inferior conjunctiva most affected

Atopic Blepharoconjunctivitis

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Atopic Blepharoconjunctivitis

Serious form of ocular allergy Usually associated with personal or family

history of atopic disease (asthma, hay fever, eczema,urticaria)

May occur throughout the year Men are more commonly affected Age at onset is late teens or early 20s Condition can last several decades

Friedlaender MH. Conjunctivitis of allergic origin: clinical presentation and differential diagnosis. Surv Ophthalmol 1993;38(suppl):105-114.

Ehlers WH, Donshik PC. Allergic ocular disorders: a spectrum of diseases. CLAO J 1992;18:117-124.

Diagnosis

Moderate to severe symptoms Ocular and periocular itching Tearing Burning Mucus discharge Photophobia

Extraocular atopy Eczema in 100% of cases Asthma in 90% Allergic rhinitis in 65%

Family history of atopy in at least 50% of patientsPower WJ, Tugal-Tutkun I, Foster CS. Long-term follow-up of patients with atopic keratoconjunctivitis. Ophthalmology 1998;105:637-642.

Foster CS, Calonge M. Atopic keratoconjunctivitis. Ophthalmology 1990;97:992-1000.

Eyelid Involvement

Dermatitis in approximately 60% of cases Blepharitis MGD Trichiasis Ectropion Entropion Madarosis Infraorbital lid edema

Foster CS, Calonge M. Atopic keratoconjunctivitis. Ophthalmology 1990;97:992-1000.

Corneal Involvement

Superficial punctate keratopathy in 100% of patients

Corneal ulceration

Neovascularization

Pannus

Stromal scarring

Management of Lid Eczema

Steroid dermatologic ointments or creams Triamcinolone 0.1% crm

or ung Loteprednol 0.5% ung Hydrocortisone 1.0% crm,

ung, gel

Case Example

Before One Week Later

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Tacrolimus 0.03% (Protopic) Ointment for Refractory Cases Inhibits T-cell activation, preventing release of

inflammatory mediators from mast cells Available as 0.03% and 0.1% ointment Effective for short or intermediate long-term

therapy (1 to 5 months) of mild to moderate atopic dermatitis

Dosed BID Most common side effect is burning, which

improves with continued use

Sakarya Y, Sakarya R. Treatment of refractory atopic blepharoconjunctivitis with topical tacrolimus 0.03% dermatologic ointment. J Ocul Pharmacol Ther 2012; 28: 94-6.

Case Report

Before treatment After 12 weeks

Clinical Pearls in Allergy Management Advise patients to avoid eye rubbing Four key locations for eczema: neck, elbows, behind

ears, behind knees When treating with topical steroid, schedule a F/U exam

within 4 weeks Confirm compliance, efficacy, symptom relief Evaluate IOP and educate about long-term

management Steroids in CL wearers:

Use b.i.d. (before and after lens wear) OR Limit duration of wear and add 3rd dose before

bedtime Ask about use of OTC and Rx eye drops

The Future of Antiinflammatories

Modified formulations (line “extensions”)Lotemax Gel (new vehicle)Prolensa (new formulation)AzaSite Plus (new combination)

New drug delivery approaches IontophoresisBiodegradation

New molecular entitiesMapracoratLifitigrast

Antiinflammatory Drugs on the HorizonAgent Sponsor Indication

Mapracorat Bausch & LombDry eye and cataract surgery inflammation

Dexamethasone iontophoresis

EyeGate Pharma Chronic dry eye

Dexamethasone Verisome injection

Icon BioscienceEliminates postop steroids

Lifitigrast SARcode BioscienceInflammation including dry eye